The early stages of an infection with pathogenic Neisseriae are determined by receptor-mediated events that finally lead to the attachment and invasion of human mucous tissues. The factors participating in this process, the pili, OPA proteins, and perhaps lipopolysaccharide (LPS), are subject to complex genetic changes that enable the pathogens to produce multiple variant forms of these factors. Antigenic variation of the pathogenic Neisseriae permits both, the escape from the human immune response and the interaction with different cells and tissues of the human host. One of the intrinsic mechanisms of antigenic variation, i.e. genetic transformation, allows exchange and recombination of virulence genes between independent Neisseria strains in multiply infected individuals. Factors, such as IgA protease, alpha-factor, and the meningococcal capsule are attributed with further striking properties, and thus render the pathogenic Neisseriae as an excellent model for the investigation of bacterial virulence.